1. LAAC: What Does the Post Marketing Data Tell Us?
Tilak K.R. Pasala, MD, MRCP
Fellow, Structural and Congenital Heart
Carlos E. Ruiz, MD, PhD, FACC, FESC, MSCAI
Professor of Cardiology in Pediatrics and Medicine
Director of Structural and Congenital Heart Disease Program
Good afternoon, My name is Tilak Pasala, I am a structural heart disease fellow with Dr. Carlos Ruiz. My topic today is LAAC: what does the post marketing data tell us?

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Tilak Pasala, MD
 I have no relevant financial relationships
Carlos E. Ruiz, MD
Grant / Research Support
Philips – St Jude Medical - Medtronic
Consulting Fees / Honoraria
Valtech – St. Jude Medical – LivaNova
Royalty / Intellectual Property Rights
Gore
Major Stock Shareholder / Equity
Vascular Therapies – MitrAssist – Entourage – BioInspire – Cardiac Implants – Valtech – Pi-Cardia – HRT - Medivalve
These are the disclosures

3. LAA closure devices in the market
WATCHMANTM Device
AMPLATZERTM AmuletTM Device
CE Mark – January 18th, 2013
Not approved in US
AMPLATZER™ Amulet™ LAA Occluder Trial (Amulet IDE): start date Aug 2016
So far – 111/1700 enrolled
FDA approval date - March 13th, 2015
CMS coverage decision - February 2016
LAAC registry – August 2016
While several devices for LAAC are approved, they are mostly in Europe. Post-market data is available for two devices, mainly – watchman device and Amlplatzer amulet device. The watchman device was approved by the FDA to reduce the risk of stroke NVAF in March 2015, although CMS coverage and LAAC registry were done much later in Feb 2016 and Aug 2016 respectively. But the company has done a tremendous job by allowing trained watchman clinical specialist in attendance at every implantation in the country – who were able to collect the data. The Amulet device obtained CE mark in January 2013 and most of the experience is in Europe. Although, Amulet IDE trial has started in Aug 2016 in the US. So far over a 100 devices have been implanted.

4. WatchmanTM device Ewolution Registry*
October 2013 – May 2015
1025 pts from 47 sites in Europe, Russia and Middle East
Initial US Clinical Experience (Post FDA approval)**
March 2015 – May 2016
3,822 consecutive patients underwent LAAC with Watchman™ implantation by 382 physicians at 169 U.S. centers
Two main studies are reported with the watchman device. The Ewolution registry reporting the experience the European experience between 2013 to 2015, over a 1000 patients have had wathman devices implanted in Europe, Russia and the middle East. In the US, post FDA approval over 3800 patients under watchman implantation.
Post FDA approval US clinical experience was reported from March 2015 to May 2016, over 3800 pts at 169 US centers are performed.
*Bergmann MW. Presented at TCT 2016
**Reddy, V. Y. et al. J Am Coll Cardiol. 2017;69(3):253-61

5. EWOLUTION Registry (Watchman)
Registry on WATCHMAN outcomes in Real-Life Utilization
In the Ewolution registry, Watchman device was implanted in 1020 pts and the 3 month follow up data from was available in 80% of these patients.
M.W. Bergmann, EuroPCR 2016 LBT 5

6. EWOLUTION: Patient characteristics

7. Watchman device: Procedural parameters
Comparison of procedural parameters
No procedures is more than all the randomized controlled trials combined.
Implantation success is superior.
Procedural duration is similar.
Devices per procedure – were similar if not less.
More importantly – 50% of procedures were preformed by newly trained operators
So, the learning curve is getting better, so much so that new operators can be trained to achieve a high success rate.
~50% of procedures performed by newly trained operators

8. Watchman device - Major complications
While that is the experience with procedural success there is a positive note in the complication rates too. All the major complications are lower in the post-approval era when compared to the randomized controlled trials despite >50% of the operators were newly trained. When we take a deeper look at the type of complications – it is important to note that the stroke and death rates are less than 0.1%
Stroke & Death ~ <0.1%

9. THE AMULET STUDY
Prospective, multicenter, international observational study.
TEE at 1-3 months
Independent echo core lab
Clinical events committee
1073 patients enrolled between Jun 2015 and Sept 2016 in 64 clinical sites in Europe, Middle East, Asia, Australia, South America
13 patients Device not implanted*
1060 patients with AMPLATZER Amulet LAA Occluder implanted
Not completed 1st database lock** (N=349)
While the experience with watchman device is very encouraging, a similar experience has been noted with the amulet device post-approval. In the Amulet Study which is a prospective, multicenter international observational study with > 1000 pts with
1-3 Month Follow Up Completed (N = 711)
Hildick-Smith D. Presented at TCT 2016

10. Amulet device: Patient characteristics
Mean ± SD or %
n=1071*
Age (years)
75 ± 8
Gender - Female
35.6%
Prior Stroke
27.1%
Prior TIA
10.6%
Heart Failure
17.4%
Diabetes
31.4%
Hypertension
84.2%
Prior History of Major Bleeding
72.5%
CHA2DS2-VASc Score > 4
65%
HAS-BLED > 3
58%
It is interesting to note that a high CHADS VASc scores were seen in 65% of the patient suggesting that even in the real world high risk patients are getting these procedures.

11. Amulet device: Procedural parameters
ACP
Registry1
Watchman
EWOLUTION2
Amulet
Study
Implant Success
97.3%
98.5%
98.8%
LAA Closure Rate
(1-3 months) < 5 mm
98.1%
99.3%
100.0%
The implant success was very high and the LAA closure rate on TEE was 100%. Amulet is superior to ACP and is comparable to watchman device.
First device selected implanted – 93%
1 Tzikas et al. EuroIntervention. 2015;10 3 Boersma et al. Eur Heart J Aug;37(31):

12. Amulet device: Major adverse events
Device/Procedure Related MAE
No. %
Death
Related to Cardiac Perforation
Related to Myocardial Infarction
Related to Cardiorespiratory Arrest 3 1
0.3%
0.1%
Stroke
Pericardial Effusion
Resulted in Pericardiocentesis
Resulted in Surgical Intervention 5 4
0.5%
0.4%
Embolization
Bleeding 10
0.9%
Other 7
0.7%
TOTAL 29
2.7%

13. Amulet device: Outcomes
Comparison with other devices
ACP
Registry1
Watchman
EWOLUTION2
Amulet
Study
Device or Procedure-Related Complications
5.0%
2.7%
Early Mortality
0.8% (30-day)
0.7% (30-day)
0.3% (7-day)
Amulet is superior to ACP and is comparable to watchman device.
1 Tzikas et al. EuroIntervention. 2015;10 3 Boersma et al. Eur Heart J Aug;37(31):

14. Summary
Procedural success was high and consistent with clinical trial results
Complications were low even with >50% of the operators being newly trained
Post-market data is encouraging and LAAO maybe a viable alternative to oral anticoagulants

15. thank you Tilak.Pasala@hackensackmeridian.org

16. Ewolution registry: Safety endpoints - 3 months
M.W. Bergmann, EuroPCR 2016 LBT 16